The metabolic fate of a number of drugs and of certain of their meabolites is being further investigated in laboratory animals and man. The purposes are to obtain more information as to differences between the species, and in particular cases the influence of disease and/or other drugs on the metabolism and the effectiveness, lack of effectiveness or aberrant toxicity in man. Quantitative accounting of single doses of phenobarbital (PB) in the rat is being pursued, including identification of presently unknown metabolites. Synthesis of PB-2-14C, 15N2 of high specific activity is being carried out, to facilitate these studies. Putative unknown metabolites will be synthesized, unlabelled, and used in isotope dilution proceduues in attempting to identify the metabolites. Identities will be further examined by mass spectrometry. Similar studies are being carried on with primidone-14C, 15N2 and hexobarbital-14C, 15N2. The latter compound is under active investigation in man, with special emphasis on the quantitation of identified metabolites in blood. In the rat and mouse we are also looking at the fate of thiobarbital-14C, 13C and of barbital-14C 15N2 and its N-methyl derivatives.